Acute pancreatitis in adults

Acute pancreatitis is an inflammation of the pancreas (and sometimes surrounding tissues) caused by the release of activated pancreatic enzymes. The main triggers of the disease are biliary tract diseases and chronic alcohol abuse.

The course of the disease varies from moderate (abdominal pain and vomiting) to severe (pancreatic necrosis and systemic inflammation with shock and multiple organ failure). The diagnosis of acute pancreatitis is based on clinical symptoms, determination of serum amylase and lipase levels. Treatment of acute pancreatitis is symptomatic, including intravenous fluids, analgesics and fasting.

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What causes acute pancreatitis?

Biliary tract diseases and alcoholism account for more than 80% of the etiologic factors of acute pancreatitis. The remaining 20% are the result of various other causes.

The exact mechanism of pancreatitis in cases of sphincter of Oddi obstruction by gallstones or microlithiasis (sludge) is not well understood, but is likely related to increased intraductal pressure. Long-term alcohol consumption (> 100 g/day for > 3-5 years) may cause accelerated precipitation of pancreatic enzyme protein in the lumen of small pancreatic ducts. Duct obstruction by these protein plugs may be the cause of early activation of pancreatic enzymes. Alcohol abuse in such patients may be the cause of acute pancreatitis due to activation of pancreatic enzymes.

Many mutations have been identified that predispose to pancreatitis. The first is an autosomal dominant mutation in the cationic trypsinogen gene, which causes pancreatitis in 80% of cases; there is a family history. Other mutations have less penetrance and are not always detectable clinically, except through genetic testing. Genetic abnormalities are responsible for cystic fibrosis, which increases the risk of recurrent acute pancreatitis.

Regardless of the etiology, pancreatic enzymes (including trypsin, phospholipase A2, and elastase) are directly activated within the gland. The enzymes damage tissue, activate complement, and initiate an inflammatory cascade, producing cytokines. This causes inflammation, edema, and sometimes necrosis. In moderate pancreatitis, inflammation is limited to the pancreas; mortality is less than 5%. In severe pancreatitis, there is marked inflammation with necrosis and hemorrhage into the gland and a systemic inflammatory response; mortality reaches 10-50%. After 5-7 days, intestinal infection may join the necrosis of pancreatic tissue.

Activated enzymes and cytokines that are released into the peritoneal cavity cause chemical peritonitis and fluid leakage into the peritoneal cavity; enzymes that enter the systemic circulation cause a systemic inflammatory response that can lead to acute respiratory distress syndrome and renal failure. Systemic effects are primarily the result of increased capillary permeability and decreased vascular tone. Phospholipase A2 is thought to damage the alveolar membranes of the lung.

In approximately 40% of patients, a collection of enzyme-rich pancreatic fluid and tissue fragments forms in and around the pancreas. In half of the cases, the process resolves spontaneously. In the remaining cases, this pathological substrate becomes infected or pseudocysts form. Pseudocysts have a fibrous capsule without an epithelial lining. Pseudocysts may be complicated by bleeding, rupture, or infection.

Death within the first few days is usually due to cardiovascular failure (with severe shock and renal failure) or respiratory failure (with hypoxemia and sometimes adult respiratory distress syndrome). Occasionally, death is due to secondary cardiac failure due to an unidentified myocardial suppressor factor. Death after a week of illness may be due to pancreatic infection or rupture of a pseudocyst.

Symptoms of acute pancreatitis

Symptoms of acute pancreatitis include persistent, aching pain in the upper abdomen, usually severe enough to require large doses of parenteral opiates. The pain radiates to the back in about 50% of cases; rarely, pain first appears in the lower abdomen. In biliary pancreatitis, pain in the left side usually develops suddenly; in alcoholic pancreatitis, pain develops over several days. The pain syndrome usually persists for several days. Sitting and bending the body forward may reduce the pain, but coughing, active movements, and deep breathing may intensify it. Nausea and vomiting are characteristic.

The patient's condition is serious, the skin is covered with sweat. The pulse rate is usually 100-140 beats per minute. Breathing is rapid and shallow. Blood pressure may be elevated or low with pronounced postural (orthostatic) hypotension. Temperature may be normal or even subnormal, but may increase from 37.7 to 38.3 "C for several hours. Consciousness may be confused, bordering on sopor. Sometimes icterus of the sclera is observed. Diaphragmatic excursion of the lungs may be reduced and signs of atelectasis may be observed.

Approximately 20% of patients have symptoms of acute pancreatitis, such as: distension in the upper abdomen caused by gastric distension or displacement of the stomach by the pancreatic inflammatory process. Destruction of the pancreatic duct may cause ascites (pancreatic ascites). Palpation is tender, most often in the upper abdomen. Moderate tenderness may be observed in the lower abdomen, but on digital examination the rectum is painless and the stool is bloodless. Moderate to severe muscle tension may be felt in the upper abdomen, but tension is rarely felt in the lower abdomen. Sometimes severe peritoneal irritation leads to tension and a board-like abdomen. Peristalsis is decreased. Grey-Turner's sign and Cullen's sign are ecchymoses on the lateral surfaces of the abdomen and in the umbilical region, respectively, and indicate extravasal hemorrhagic exudate.

The development of an infection in the pancreas or in the peripancreatic fluid is indicated by phenomena of general intoxication with an increase in temperature and the level of red blood cells, or if the deterioration of the condition occurs after the initial period of stabilization of the course of the disease.

Diagnosis of acute pancreatitis

Acute pancreatitis should be suspected in the presence of severe abdominal pain, especially in individuals who abuse alcohol or in patients with known gallstones. Similar symptoms of acute pancreatitis may be observed in perforated gastric or duodenal ulcers, mesenteric infarction, strangulating intestinal obstruction, dissecting aortic aneurysm, biliary colic, appendicitis, diverticulitis, posterior myocardial infarction, hematoma of the abdominal wall muscles, and splenic injury.

The diagnosis is made by clinical examination, serum markers (amylase and lipase), and the absence of other causes of symptoms. In addition, a wide range of investigations are performed, usually including a complete blood count, electrolytes, calcium, magnesium, glucose, blood urea nitrogen,creatinine, amylase, and lipase. Other routine investigations include ECG and serial abdominal examinations (chest, supine, and upright abdomen). Urine trypsinogen-2 has a sensitivity and specificity of more than 90% for acute pancreatitis. Ultrasound and CT are generally not highly specific for the diagnosis of pancreatitis, but are often used to evaluate acute abdominal pain and are indicated when pancreatitis is diagnosed.

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Laboratory diagnostics of acute pancreatitis

Serum amylase and lipase levels increase on the first day of acute pancreatitis and return to normal within 3 to 7 days. Lipase is more specific for pancreatitis, but both enzymes may be elevated in renal failure and other abdominal diseases (eg, perforated ulcer, mesenteric vascular occlusion, intestinal obstruction). Other causes of elevated serum amylase include salivary gland dysfunction, macroamylasemia, and tumors that secrete amylase. Amylase and lipase levels may remain normal if acinar tissue has been destroyed during previous episodes of the disease, resulting in decreased adequate enzyme secretion. The serum of patients with hypertriglyceridemia may contain circulating inhibitor, requiring dilution before serum amylase increases.

Amylase/creatinine clearance is not sensitive or specific for diagnosing pancreatitis. It is commonly used to diagnose macroamylasemia in the absence of pancreatitis. In macroamylasemia, serum immunoglobulin-bound amylase produces a false-positive result due to elevated serum amylase.

Fractionation of total serum amylase into pancreatic type (p-type) and salivary type (s-type) isoamylase increases the diagnostic value of serum amylase levels. However, the p-type level also increases in renal failure, as well as in other severe diseases of the abdominal organs, in which amylase clearance is altered.

The white blood cell count usually increases to 12,000-20,000/μl. Fluid leakage into the peritoneal cavity can significantly increase the hematocrit to 50-55%, thus indicating severe inflammation. Hyperglycemia may be observed. The serum calcium concentration decreases already on the first day of the disease due to secondary formation of Ca "soap" as a result of excessive production of free fatty acids, especially under the action of pancreatic lipase. Serum bilirubin increases in 15-25% of patients due to pancreatic edema and compression of the common bile duct.

Instrumental diagnostics of acute pancreatitis

Plain abdominal radiography may reveal calcifications in the pancreatic ducts (indicating previous inflammation and hence chronic pancreatitis), calcified gallstones, or focal bowel obstruction in the left upper quadrant or mesogastrium (a "dilated loop" of small bowel, dilated transverse colon, or duodenal obstruction). Chest radiography may reveal atelectasis or pleural effusion (usually left-sided or bilateral, but rarely limited to the right pleural space).

If the studies are non-diagnostic, an ultrasound should be performed to diagnose cholelithiasis or dilatation of the common bile duct (indicating biliary tract obstruction). Swelling of the pancreas may be visualized, but gas in the intestine often obscures the pancreas.

CT with intravenous contrast usually allows identification of necrosis, fluid collections, or pseudocysts in the diagnosis of pancreatitis. This study is especially recommended in cases of severe pancreatitis or development of complications (e.g., hypotension or progressive leukocytosis and fever). Intravenous contrast facilitates recognition of pancreatic necrosis, but it may cause pancreatic necrosis in areas of low perfusion (i.e., ischemia). Therefore, CT with contrast should be performed only after adequate fluid resuscitation and correction of dehydration.

If infection is suspected, percutaneous puncture of the cyst, fluid accumulation area or necrosis under CT control with fluid aspiration, Gram staining and bacteriological culture is indicated. The diagnosis of acute pancreatitis is confirmed by positive blood culture results, and especially by the presence of retroperitoneal pneumatization on abdominal CT. The introduction of MR cholangiopancreatography (MRCP) into practice makes instrumental examination of the pancreas simpler.

Treatment of acute pancreatitis

Adequate infusion therapy is important; sometimes up to 6-8 L/day of fluids containing the necessary electrolytes is required. Inadequate infusion therapy of acute pancreatitis increases the risk of developing pancreatic necrosis.

Exclusion of food intake is indicated until signs of inflammation have subsided (i.e., pain and tenderness on palpation have disappeared, serum amylase has returned to normal, appetite has returned, and subjective improvement has occurred). Fasting may be necessary for several days in moderate pancreatitis, up to several weeks in severe cases. To compensate for the lack of enteral nutrition in severe cases, patients should be switched to total parenteral nutrition in the first few days.

Treatment of pain in acute pancreatitis requires parenteral opiates, which must be given in adequate doses. Although morphine may cause spasm of the sphincter of Oddi, this is of questionable clinical significance. Antiemetics (eg, prochlorperazine 5-10 mg IV every 6 hours) should be given to relieve vomiting. Nasogastric intubation is required if severe vomiting or symptoms of intestinal obstruction persist.

Parenteral H2 blockers or proton pump inhibitors are administered _. Attempts to reduce pancreatic secretion with medications (eg, anticholinergics, glucagon, somatostatin, octreotide) have no proven efficacy.

Patients with severe acute pancreatitis require treatment in the intensive care unit, especially in the presence of hypotension, oliguria, Ranson score 3, APACHE II 8, or pancreatic necrosis > 30% on CT. In the intensive care unit, vital signs and urine output should be monitored hourly; metabolic parameters (hematocrit, glucose, and electrolytes) should be determined every 8 hours; arterial blood gases should be determined as needed; in case of unstable hemodynamics or to determine the volume of fluid to be transfused, linear central venous pressure or a Swan-Ganz catheter should be measured every 6 hours. Complete blood count, platelet count, coagulation parameters, total protein and albumin, blood urea nitrogen, creatinine, Ca, and Mg should be determined daily.

Hypoxemia is treated with humidified oxygen via mask or nasal tubes for acute pancreatitis. If hypoxemia persists or adult respiratory distress syndrome develops, assisted ventilation is indicated. If glucose levels rise above 170 to 200 mg/dL (9.4 to 11.1 mmol/L), cautious subcutaneous or intravenous insulin is given with close monitoring. Hypocalcemia requires no treatment unless neuromuscular irritability develops; 10 to 20 mL of 10% calcium gluconate in 1 L of intravenous fluid is given over 4 to 6 hours. Chronic alcoholics and patients with known hypomagnesemia should receive magnesium sulfate 1 g/L of transfused fluid, for a total of 2 to 4 g until electrolyte levels are normal. If renal failure develops, serum magnesium levels should be monitored closely and intravenous magnesium should be given cautiously. With the restoration of normal Mg levels, serum Ca levels return to normal.

Prerenal azotemia requires increased infusion therapy. If renal failure develops, dialysis (usually peritoneal) is indicated.

Antibiotic prophylaxis with imipenem may prevent infection of sterile pancreatic necrosis, although its effect on mortality is unclear. Infected areas of pancreatic necrosis require surgical debridement, but infected fluid collections around the pancreas may be drained percutaneously. Pseudocysts that fill rapidly, become infected, bleed, or are at risk of rupture require drainage. The choice of drainage method (percutaneous, surgical, or endoscopic) depends on the location of the pseudocyst and hospital capacity. Peritoneal lavage to remove activated pancreatic enzymes and inflammatory mediators has no proven efficacy.
Surgical treatment of acute pancreatitis within the first few days is justified in severe blunt or penetrating trauma and progressive biliary pathology. Although more than 80% of patients with biliary pancreatitis pass the stone spontaneously, ERCP with sphincterotomy and stone removal is indicated in patients who do not improve after 24 hours of treatment. Patients who resolve spontaneously require elective laparoscopic cholecystectomy. Elective cholangiography remains controversial.

What is the prognosis for acute pancreatitis?

Edematous acute pancreatitis has a mortality rate of less than 5%. In necrotic and hemorrhagic pancreatitis, mortality reaches 10-50%. In the case of infection, without extensive surgical treatment or drainage of the infected area, mortality usually reaches 100%.

CT findings correlate with prognosis. If CT is normal or shows only moderate pancreatic edema (Balthazar class A or B), the prognosis is favorable. In patients with peripancreatic inflammation or fluid accumulation in one area (class C and D), an abscess develops in 10-15% of cases; with fluid accumulation in two or more areas (class E), the risk of abscess formation is more than 60%.

Ranson prognostic signs help to predict the course of acute pancreatitis. Five Ranson signs can be determined on admission: age >55 years, serum glucose >200 mg/dL (>11.1 mmol/L), serum LDH >350 IU/L, AST >250 U, and WBC >16,000/μL. The remaining parameters are determined within 48 hours of admission: decrease in Hct >10%, increase in BUN >5 mg/dL (>1.78 mmol/L), serum Ca <8 mg/dL (<2 mmol/L), pO2 <60 mmHg (<7.98 kPa), base deficit >4 mEq/L (>4 mmol/L), and estimated fluid sequestration >6 L. Acute pancreatitis has a variable mortality risk, which increases with the number of positive signs: if less than three signs are positive, the mortality is less than 5%; if three or four are positive, the mortality can be 15-20%.

APACHE II scores calculated on day 2 after hospitalization also correlate with the prognosis of acute pancreatitis.